Breast cancer is the most frequently diagnosed cancer (excluding skin cancer) in women, and is the second leading cause of cancer death among women in the U.S. Currently, one woman in seven will develop breast cancer in her lifetime. Surgical intervention is warranted in most cases. However, as tumors are being detected at increasingly earlier stages, new methods for less invasive and more focal treatments are warranted. In sharp contrast with its premise, the translation of high-intensity focused ultrasound (HIFU) to the clinic has been comparatively anemic due to the unreliable (B-mode-based) or extremely costly and slow (MRI-based) monitoring techniques available. There has thus been an urgent need for a simple, cost- efficient technology that can reliably and efficiently monitor HIFU treatment and thereby ensure its clinical translation. In order to address both needs and maintain the low cost of HIFU while preserving all its advantages, we have developed the radiation-force-based technique of Harmonic Motion Imaging (HMI) that can be used seamlessly with HIFU for simultaneous tumor targeting and generation and monitoring of ablation, namely HMI for Focused Ultrasound (HMIgFUS). In the proposed study, we will integrate the HMIgFUS into a clinical system that will facilitate translation of HMIFU for the focal, thermal treatment of breast tumors. The underlying hypothesis is that HMIgFUS using parallel beamforming will be capable of optimally monitoring HIFU ablation in a clinical setting where speed of application is key. The team assembled encompasses ultrasound, breast imaging, breast surgery, mouse tumor models and histopathological analysis. Our group has demonstrated that motion estimation using parallel beamforming is feasible 1) at extremely high framerates (up to 5000 fps) ensuring highest quality of motion estimation including 2) high precision displacements, 3) coherent compounding for SNR increase, 4) 2D capability as well as 5) real-time implementation. Such a reliable monitoring technique could prove pivotal in rendering an entirely noninvasive treatment accessible to a wide population of breast cancer patients for the first time by propelling it into fast and reliable outpatient procedure for the focal treatment of benign or small, non-metastatic breast cancer, thus minimizing mortality and risk.